CSRD Research Career Scientist Award Application

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Dr. Erin Hazlett is currently a VA Research Career Scientist (RCS) at the James J. Peters VA Medical Center (JJPVAMC). This is her first RCS Award renewal application. Schizophrenia (Sz)-spectrum disorders and suicidal behavior are major public health problems affecting Veterans. Each year, the VA provides care to approximately 100,000 Sz patients, accounting for nearly 12% of the VA’s total healthcare costs. In 2019, Veteran suicides were double that of civilians in the United States. The PI’s ongoing clinical cognitive neuroscience research at the VA uses neuroimaging and psychophysio- logical approaches and primarily focuses on these two areas: elucidating the neurobiology of Sz and suicidal behavior. Identification of promising new targets for intervention in Sz and suicide prevention are critically important goals of the VA. The PI’s track record of federal funding and peer-reviewed publications in these two areas has helped advance the field. Suicidal behavior in Veterans: Dr. Hazlett’s current VA Collaborative CSR&D/BLR&D Merit Award investigates the underlying neurobiology of impulsivity in Veterans at low and high risk for suicide. Using task- based fMRI, she examines the correlates of motor and cognitive impulsivity in healthy-control (HC) Veterans and pathological severity of impulsivity in Veterans with major depressive disorder (MDD) with and without a history of suicide attempt(s) (SA) and mild traumatic brain injury (mTBI). In all, five groups of Veterans are being studied: HC, SA-mTBI-, SA+mTBI-, SA-mTBI+, SA+mTBI+. Our collaborative VA sites are studying an animal model of mTBI (East Orange, NJ VA), collecting identical behavioral impulsivity data in acutely suicidal inpatients (Indy VA), and assisting with rigorous diagnostic/symptom severity assessments (Denver VA). Blood is being studied (Indy VA) in participants to examine inflammation and epigenetics related to suicidal behavior. This work promises to help uncover the mechanisms by which biological and psychological factors give rise to suicidal behavior and may aid in prospectively identifying Veterans at greatest risk for suicide. The second component is funded by a new VA RR&D SPiRE grant and aims to collect pilot data to test the feasibility and acceptability of an adjunctive neuroplasticity-based Cognitive Remediation (CR) intervention on key treatment targets delivered via telehealth in a sample of 36 Veterans with MDD and a history of SA. It will test the effects of an evidence-based CR therapy augmented with manualized “Bridging” sessions on transfer and practice of cognitive control and decision-making/problem-solving strategies for real-world situations and problems, including those that trigger suicidal thoughts. This is the first implementation of this intervention in Veterans with MDD and suicidal behavior. Consistent with the SPiRE mechanism, this study is high risk, but it has high potential impact and promise to help improve quality of life for Veterans at high risk for suicide. If results are encouraging, Dr. Hazlett will submit a multi-site VA RCT Merit in the Spring of 2023. Schizophrenia (Sz)-spectrum disorders: Dr. Hazlett’s current NIMH R01 and supplement grants involve the first longitudinal design to study schizotypal personality disorder (SPD)—a disorder similar to Sz but with fewer and attenuated abnormalities, thus representing an important, yet understudied intermediate Sz- spectrum phenotype. Examination of abnormalities in SPD will provide information regarding etiology, genetics, treatment, and risk factors associated with psychosis. This is the first longitudinal study to utilize multimodal- MR imaging across the continuum of Sz-spectrum disorders from HCs to SPD to Sz and examine changes in neural circuitry in relationship to impairments in symptom severity, neurocognition, and functional outcome. Impact: This Research Career Scientist Award will allow the PI to augment her highly collaborative VA research with VA clinician-scientists and mentoring of promising VA MIRECC Fellows. The PI’s goal is to further expand her MRI research program in Sz and suicidal behavior at the JJPVAMC and beyond.